Research: Our research group is focused on investigating the genetic basis for human lung cancer and to develop new strategies for clinical trials. We have studied the role of the RB tumor suppressor pathway in human cancer and have demonstrated that the RB/p16 tumor suppressor pathway is inactivated in 100% of small cell lung cancer (SCLC) and non-SCLC. We are investigating functional properties of the RB tumor suppressor protein using mutant alleles isolated from patients with lung cancer and from families linked with the phenoytpe of incomplete penetrance. This will include analyses of site-specific phosphorylation patterns and protein binding properties. In addition, using mutant RB transgenes driven by the endogenous RB promoter we have developed a mouse model for incomplete penetrance. We have also identified caspase-mediated cleavage of the C-terminal 42 amino acids of RB at the onset of apoptosis and we have initiated a project to determine if this cleavage event is central to regulation of programmed cell death. In addition, we are studying the patterns of gene inactivation that discriminate between the neuroendocrine and non-neuroendocrine lung tumors. To study the genetic basis for selected lung tumors we have begun to collect samples from young patients with lung cancer. As part of this research effort we have begun a project to study the molecular basis for the genesis of lung mucoepidermoid carcinoma.